Abstract
BackgroundSilicosis has been topping the list of high-incidence occupational diseases in developing countries and cannot be completely cured. Recent advances in stem cell research have made possible the treatment of various diseases including lung fibrosis. The application of stem cell therapy in occupational diseases, in particular the use of adipose-derived mesenchymal stem cells (AD-MSCs) in treatment of silicosis, has not yet been reported. The aim of the study is to explore the intervening effect of silica-induced lung fibrosis in rats.MethodsIn this study, we investigated the anti-pulmonary fibrosis effects of the transplantation of AD-MSCs in rats in which lung fibrosis was induced by oral tracheal intubation with silica suspension. Twenty rats were divided into four groups: control group (n = 5), exposure group (n = 5), vehicle group (n = 5) and treatment group (n = 5). AD-MSCs were given to rats after exposure to silica for 24 h. Twenty-eight days after AD-MSC transplantation, we examined the organ coefficient, inflammatory cytokines, apoptosis, pathological and fibrotic changes in lung tissue.ResultsResults showed that exposure to silica for 28 days induced an increase of the lung coefficient with significant pulmonary fibrosis. Treatment with AD-MSC transplantation led to a remissive effect on pulmonary fibrosis. We found that after AD-MSC transplantation the inflammatory response decreased and Caspase-3 protein expression significantly decreased with a significant increase of the Bcl-2/Bax ratio.ConclusionsAnti-inflammatory and anti-apoptosis of AD-MSCs may play important roles in their anti-pulmonary fibrosis effect. Our data suggest that transplantation of AD-MSCs holds promise for potential interference in the formation of silicosis through regulating inflammatory and apoptotic processes.
Highlights
Silicosis has been topping the list of high-incidence occupational diseases in developing countries and cannot be completely cured
Twenty adult male Sprague Dawley (SD) rats were randomly divided into four groups: control group (n = 5), which were normally fed; exposure group (n = 5), which were exposed to silica; vehicle group, (n = 5), in which Dulbecco’s modified Eagle’s medium (DMEM) culture medium was administered by intravenous injection 24 h after silica exposure; and treatment group (n = 5), which received 5 × 105 Adipose-derived mesenchymal stem cell (AD-mesenchymal stem cells (MSCs)) by intravenous injection 24 h after exposure to Culture and identification of stem cells AD-MSCs from adipose tissue of 4-week-old healthy male adult SD rats (n = 3) were isolated and cultured according to a previous report with slight modifications [24]
Consistent with several previous studies using fetal membrane-derived stem cells and preconditioned Bone marrow-derived mesenchymal stem cell (BM-MSC) transplantations as bleomycin-induced pulmonary fibrosis therapies [27, 28], we demonstrated that AD-MSC transplantation can reduce the pulmonary inflammatory response of rats after oral tracheal intubation with silica suspension, indicating the migration and homing of AD-MSCs toward the lungs through intravenous infusion to affect the inflammatory response to silica exposure
Summary
Silicosis has been topping the list of high-incidence occupational diseases in developing countries and cannot be completely cured. Recent advances in stem cell research have made possible the treatment of various diseases including lung fibrosis. The application of stem cell therapy in occupational diseases, in particular the use of adipose-derived mesenchymal stem cells (AD-MSCs) in treatment of silicosis, has not yet been reported. Pathological characteristics of silicosis include alveolar epithelial cell injury and the formation of pulmonary fibrosis, but the mechanisms of silicosis are not fully clear. It is believed that inflammatory-related and apoptosis-related mechanisms play important roles in lung injury induced by silica dust and intervening/therapeutic routes targeting these pathways have been explored. Much progress has been made in understanding the mechanisms of mesenchymal stem cells (MSCs) in the aspects of regulating immunity and tissue remodeling in animal models of lung fibrosis [3]. In lung tissue rescue and repair, adult MSCs have been proposed to be a valuable therapeutic option due to their availability, immunomodulatory effects and anti-apoptotic and antiinflammatory properties [4]
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